The long-term goals of this HIV research program are twofold to elucidate the mechanisms and timing of in utero maternal-fetal HIV transmission, and to establish an animal model, demonstrating a high incidence of transmission, with which to test the efficacy of therapeutic agents to decrease maternal-fetal HIV transmission. We have made significant progress toward achieving the first goal by using HIV-2 strain 287, which is highly pathogenic in the macaque, to infect the unique, chronically catheterized maternal-fetal macaque model. This HIV-2287-infected maternal-fetal model permits frequent and simultaneous sampling of maternal blood, fetal blood and the amniotic fluid in monitoring the immunological and virological response profiles of the dam and the fetus without the confounding factor of maternal blood contamination always encountered in human studies. Our data indicate that the extent of maternal virological response and mucosal exposure of the fetus through HIV in th e amniotic fluid may predict the outcome of in utero HIV transmission. In addition, we found that suppression of maternal virus load with a highly active antiviral drug combination therapy may reduce the risk of fetal infection. FUNDING NIH grants RR00166 and HL56548. Unadkat, J.D., Larsen K., Bui, T., Sherbert, C., Finn, E., Nosbisch, C., Schmidt, A., Anderson, D., Agy, M.B., Morton, W.R., and Ho, R.J.Y., 1998. Triple drug combination therapy, AZT, DDI and indinavir prevent mother-to-fetus HIV transmission preliminary results with HIV-2 in macaques. J. Med. Primatol. 27:47, 1998.